rs10844318

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001278464.2(DNM1L):c.957A>G(p.Thr319Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,406 control chromosomes in the GnomAD database, including 15,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1555 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13584 hom. )

Consequence

DNM1L
NM_001278464.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.749

Publications

11 publications found

Variant links:

Genes affected

DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

DNM1L Gene-Disease associations (from GenCC):

encephalopathy due to mitochondrial and peroxisomal fission defect
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1
Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
optic atrophy 5
Inheritance: AD Classification: STRONG Submitted by: G2P
autosomal dominant optic atrophy, classic form
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

DNM1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-32722472-A-G is Benign according to our data. Variant chr12-32722472-A-G is described in ClinVar as Benign. ClinVar VariationId is 260168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.749 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2 link	c.957A>G	p.Thr319Thr	synonymous_variant	Exon 10 of 21	ENST00000553257.6	NP_001265393.1	O00429-6B4DYR6
DNM1L	NM_012062.5 link	c.918A>G	p.Thr306Thr	synonymous_variant	Exon 9 of 20	ENST00000549701.6	NP_036192.2	O00429-1B4DYR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6 link	c.957A>G	p.Thr319Thr	synonymous_variant	Exon 10 of 21	2	NM_001278464.2	ENSP00000449089.1		O00429-6
DNM1L	ENST00000549701.6 link	c.918A>G	p.Thr306Thr	synonymous_variant	Exon 9 of 20	1	NM_012062.5	ENSP00000450399.1		O00429-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21495

AN:

152092

Hom.:

1551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0735

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0892

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.123

AC:

30841

AN:

250954

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.0779

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0970

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.134

AC:

195843

AN:

1460196

Hom.:

13584

Cov.:

AF XY:

0.134

AC XY:

97565

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.175

AC:

5856

AN:

33430

American (AMR)

AF:

0.0838

AC:

3747

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4242

AN:

26124

East Asian (EAS)

AF:

0.0708

AC:

2808

AN:

39648

South Asian (SAS)

AF:

0.112

AC:

9646

AN:

86208

European-Finnish (FIN)

AF:

0.100

AC:

5339

AN:

53366

Middle Eastern (MID)

AF:

0.176

AC:

888

AN:

5044

European-Non Finnish (NFE)

AF:

0.139

AC:

154925

AN:

1111382

Other (OTH)

AF:

0.139

AC:

8392

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

8203

16406

24610

32813

41016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5500

11000

16500

22000

27500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.141

AC:

21500

AN:

152210

Hom.:

1555

Cov.:

AF XY:

0.139

AC XY:

10335

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.169

AC:

7017

AN:

41520

American (AMR)

AF:

0.122

AC:

1866

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

557

AN:

3468

East Asian (EAS)

AF:

0.0737

AC:

382

AN:

5184

South Asian (SAS)

AF:

0.104

AC:

503

AN:

4820

European-Finnish (FIN)

AF:

0.0892

AC:

945

AN:

10594

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9610

AN:

68016

Other (OTH)

AF:

0.150

AC:

317

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

960

1921

2881

3842

4802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.140

Hom.:

1468

Bravo

AF:

0.146

Asia WGS

AF:

0.105

AC:

366

AN:

3476

EpiCase

AF:

0.149

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Optic atrophy 5

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.6

(source)

DANN

Benign

0.73

PhyloP100

-0.75

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over